How do you screen for exocrine pancreatic insufficiency (EPI)?

Screening for Exocrine Pancreatic Insufficiency

The fecal elastase-1 test is the most appropriate initial screening test for EPI and should be performed on semi-solid or solid stool specimens, with levels <100 μg/g providing good evidence of EPI. 1

Who to Screen

High-Risk Populations (Screen Proactively)

• Chronic pancreatitis 1
• Relapsing acute pancreatitis 1
• Pancreatic ductal adenocarcinoma 1
• Cystic fibrosis 1
• Previous pancreatic surgery 1

Moderate-Risk Populations (Consider Screening)

• Duodenal diseases (celiac disease, Crohn's disease) 1
• Previous intestinal surgery 1
• Longstanding diabetes mellitus 1
• Hypersecretory states (Zollinger-Ellison syndrome) 1

Clinical Features That Should Prompt Screening

Look for these specific manifestations: 1

• Steatorrhea (with or without diarrhea)
• Unintentional weight loss
• Bloating and excessive flatulence
• Fat-soluble vitamin deficiencies (A, D, E, K)
• Protein-calorie malnutrition

Diagnostic Testing Algorithm

First-Line Test: Fecal Elastase-1

Test specifications: 1

• Must be performed on semi-solid or solid stool (liquid/watery stool causes false positives) 2
• Can be performed while patient is on pancreatic enzyme replacement therapy 1

Interpretation: 1, 2

• <100 μg/g: Good evidence of EPI (high specificity at this cutoff) 3
• 100-200 μg/g: Indeterminate for EPI
• >200 μg/g: Normal pancreatic function

Performance characteristics: The test has pooled sensitivity of 0.94 and specificity of 0.69 at the 200 μg/g cutoff, but lowering the threshold to 100 μg/g improves specificity to 0.82 while maintaining sensitivity of 0.88. 3 In low pre-test probability settings (5%), the false-negative rate is only 1.1%, making it excellent for ruling out EPI, though the false-positive rate of 11% limits its utility for ruling in disease. 4

When Fecal Elastase is Insufficient

Fecal fat testing (rarely needed): 1

• Requires high-fat diet during testing
• Quantitative 72-hour collection is burdensome and impractical for routine use 1
• Consider only when clinical features are inconclusive or when assessing inadequate response to treatment 1

Cross-sectional imaging (CT, MRI, endoscopic ultrasound): 1

• Cannot diagnose EPI but identifies underlying pancreatic pathology 1
• End-stage calcific pancreatitis or significant pancreatic atrophy correlates with EPI presence 1
• Normal imaging correlates with absence of EPI 1

Breath tests and direct pancreatic function tests: 1

• Hold promise but not widely available in the United States 1
• Direct tests (endoscopic pancreatic secretion collection) are most accurate but invasive and time-consuming 1

Critical Pitfalls to Avoid

Do NOT use therapeutic trial of pancreatic enzymes for diagnosis: 1 Symptomatic improvement with enzyme therapy is unreliable because nonspecific symptoms (bloating, gas, foul-smelling stools) may improve due to placebo effect or may mask other disorders like celiac disease, causing diagnostic delays. 1

Avoid testing on liquid/watery stool: This produces false-positive results on fecal elastase testing. 2

Do NOT rely on serum pancreatic enzyme levels: These are unreliable if the patient has ongoing pancreatic inflammation. 1

Why This Matters for Patient Outcomes

Untreated EPI leads to: 1

• Complications from fat malabsorption
• Progressive malnutrition
• Negative impact on quality of life
• Increased morbidity

Early identification through appropriate screening in high-risk populations prevents these complications and allows timely initiation of pancreatic enzyme replacement therapy. 1